Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio
Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio
复制标题
DOI：
10.1667/rr15531.1
复制
发表时间：
2020-05
影响因子：
3.4
通讯作者：
Hongyu Zhu;A. McNamara;S. McMahon;J. Ramos-Méndez;N. Henthorn;B. Faddegon;K. Held;J. Perl;Jun-Li Li-Jun-Li-Li-119581580;H. Paganetti;J. Schuemann
中科院分区：
文献类型：
--
作者：
Hongyu Zhu;A. McNamara;S. McMahon;J. Ramos-Méndez;N. Henthorn;B. Faddegon;K. Held;J. Perl;Jun-Li Li-Jun-Li-Li-119581580;H. Paganetti;J. Schuemann
细胞对电离辐射的反应仍然是癌症放射治疗中的重要研究兴趣，而 DNA 被认为是大多数辐射生物效应的关键靶点。事件粒子可以在短时间内通过物理和化学相互作用造成最初的 DNA 损伤。最初的 DNA 损伤可以通过细胞周期不同阶段的不同途径进行修复。 DNA 损伤的错误修复会导致基因组重排，并导致突变和染色体畸变，这些都是细胞死亡的驱动因素。这项工作提出了一项模拟 0.5-500 MeV 能量（LET 为 60-0.2 keV/μm）质子辐照后细胞反应的综合研究。在 TOPAS-nBio 中实现了具有分形 DNA 几何形状的整个细胞核模型，用于初始 DNA 损伤模拟。 TOPAS-nBio 中的默认物理和化学模型用于描述原子核内初级粒子、次级粒子和辐射分解产物的相互作用。发现初始 DNA 双链断裂 (DSB) 产量从 0.2 keV/μm 低线性能量转移 (LET) 下的 6.5 DSB/Gy/Gbp 增加到 60 keV/μm 高 LET 下的 21.2 DSB/Gy/Gbp。应用机械修复模型来预测DNA损伤修复的特征和染色体畸变的剂量反应。结果发现，超过 95% 的 DSB 在前 24 小时内得到修复，并且误修复的 DSB 分数随着 LET 迅速增加，在 60 keV/μm 时达到 15.8%，估计染色体畸变检测阈值为 3 Mbp。计算了质子辐照后双着丝粒和无着丝粒碎片的产量以及微核形成的剂量响应，并与实验结果进行了比较。
The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages can undergo repair via different pathways available at different stages of the cell cycle. The misrepair of DNA damage results in genomic rearrangement and causes mutations and chromosome aberrations, which are drivers of cell death. This work presents an integrated study of simulating cell response after proton irradiation with energies of 0.5–500 MeV (LET of 60–0.2 keV/µm). A model of a whole nucleus with fractal DNA geometry was implemented in TOPAS-nBio for initial DNA damage simulations. The default physics and chemistry models in TOPAS-nBio were used to describe interactions of primary particles, secondary particles, and radiolysis products within the nucleus. The initial DNA double-strand break (DSB) yield was found to increase from 6.5 DSB/Gy/Gbp at low-linear energy transfer (LET) of 0.2 keV/µm to 21.2 DSB/Gy/Gbp at high LET of 60 keV/µm. A mechanistic repair model was applied to predict the characteristics of DNA damage repair and dose response of chromosome aberrations. It was found that more than 95% of the DSBs are repaired within the first 24 h and the misrepaired DSB fraction increases rapidly with LET and reaches 15.8% at 60 keV/µm with an estimated chromosome aberration detection threshold of 3 Mbp. The dicentric and acentric fragment yields and the dose response of micronuclei formation after proton irradiation were calculated and compared with experimental results.